The invention is concerned with novel peptide renin inhibitors and synthesis of intermediate 4-hydroxyacyl units.
Peptide renin inhibitors are disclosed in the literature [See e.g. U.S. Pat. No. 4,384,994; European Patent Application No. 0,077,029; U.S. Pat. No. 4,397,786; Boger et al. Nature 303: 81-84 (1983)]. One class of such inhibitors contains the statine type amino acid residue of the formula: ##STR3## which is (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid and its analogs.
Peptide renin inhibitors have been discovered containing a 4-hydroxyacyl group of the formula: ##STR4## attached to the nitrogen of the statine type amino acid. Synthesis of specific examples of this 4-hydroxyacyl group where R.sup.1 is nitrogen have been described in the literature (see e.g. European Patent Application EP45665; Holladay and Rich, Tetrahedron Lett., 1983, 24, 4401; Szelke et al., Proceedings of the American Peptide Symposium (8th), 1983, 579). These synthesis do not provide easy access to all individual diastereomers nor do they provide compatability with a wide range of substituents R.sup.2 and R.sup.3. A new stereocontrolled synthesis of this 4-hydroxyacyl group which does provide these features has been discovered.